This project is concerned with those factors, dietary and otherwise, that influence the trypsin and chymotrypsin feedback regulation of pancreatic secretion in the rat. The evidence to date indicates that the removal of trypsin from the intestine stimulates secretion only if from the upper one-third of the small intestine. The depression of secretion by trypsin also occurs only in the upper one-third of the intestine and only trypsin with an available active site causes depression of secretion. Trypsin appears to exert its effect from the lumen of the intestine rather than directly on the pancreas. We intend to investigate the mode of action of trypsin, i.e., how it exerts its pancreatic effect from the intestine. Also of interest is that free amino acids may not have the pancreatic stimulating effect of intact protein. The significance of this in regard to a physiological role for trypsin regulation of pancreatic secretion will also be studied.